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Page 6 of 33 Berardi et al. J Cancer Metastasis Treat 2019;5:79 I http://dx.doi.org/10.20517/2394-4722.2019.008

According to serum osmolality status, hyponatremia can be divided into [43,44] :
- Hypotonic is characterized by reduced serum osmolality, due to an excess of free water compared to the
sodium. This condition might be induced by an excessive water intake (e.g., primary polydipsia) or by a
compromised renal water excretory capacity (SIAD).
- Hypertonic is characterized by increased serum osmolality (e.g., in glycemic decompensation).
- Isotonic is characterized by normal serum osmolality, often secondary to an artificially hyponatremia
(pseudohyponatremia) due to elevated serum solutes concentrations (e.g., hyperlipidemia).

Management
A correct and timely diagnosis of hyponatremia is essential to setting up a rapid therapy and improving the
prognosis of cancer patients. Diagnosis can occur from clinical suspicion, but it is essential for clinicians
monitoring serum/plasma sodium level in all cancer patients, in order to promptly correct this electrolyte
disturbance, when present, even in the case of symptoms’ absence. Hyponatremia symptoms are often
[1]
absent or generic and closely related to hyponatremia grade and onset speed .

Patients with mild and/or chronic hyponatremia are often asymptomatic or present blurred symptoms that
can be misunderstood or imputed to other causes (e.g., dizziness, postural instability, and asthenia).

Patients with severe and/or acute hyponatremia can present different symptoms (from gastrointestinal
symptoms such as lack of appetite, nausea, and vomiting to neurological disorders such as headache,
irritability, attention deficit, confusion, gait disturbances, and muscle cramps), including life-threatening
conditions (bulbar paralysis, lethargy, convulsions, encephalic brain herniation, coma, and cardio-
respiratory arrest).

Diagnosis of hyponatremia requires routine laboratory tests. For a correct therapeutic approach, it is crucial
to identify the underlying causes, thus lab assessment should also include plasma and urine osmolality, ECV
status evaluation, and urinary sodium concentration to obtain a correct differential diagnosis [Figure 1].

In particular, due to different therapeutic options, it is fundamental to exclude SIAD. SIAD diagnosis is
diagnosis of exclusion, for which the main criteria are:
- Presence of hyponatremia (< 135 mEq/L).
- Normal ECV.
- Lower serum osmolality (< 275 mOsm/kg).
- Altered urine osmolality (> 100 mOsm/kg).
- Elevated urine sodium concentration (> 30 mmol/L).
- Normal renal function.
- Normal adrenal and thyroid function.
- No use of diuretics.

The therapeutic approach depends on etiology, presence of symptoms, and grade of hyponatremia [Figure 1].
Regardless of hyponatremia’s cause, it is important to remember that an effective and prompt correction of
[45]
serum sodium concentration improves the outcome of cancer patients .
Treatment options include fluid restriction, diuretics, saline solution administration, and vaptans (selective
vasopressin receptor antagonists).

Fluid restriction is a difficult therapeutic choice since it is associated with poor compliance because cancer
patients often need abundant hydration for oncological therapies. Furthermore, several days are required to
correct serum sodium concentrations. In the case of ECV, isotonic saline infusion should be preferred.